Support is requested for a Keystone Symposia meeting entitled The Modes of Action of Vaccine Adjuvants, organized by Philippa C. Marrack, Steven Reed and Robert A. Seder. The meeting will be held in Seattle, Washington from October 8-13, 2014. Globally, vaccines are the most practical and cost-effective medical interventions in limiting morbidity and mortality against infections. Key to vaccine efficacy is th inclusion of adjuvants that improve the magnitude and breadth of the immune response and the establishment of immunological memory. Current used adjuvants include nucleic acids, insoluble aluminum salts (alum), oil-in- water emulsions (MF-59) and formulated toll-like receptor ligands (MPL-TLR4). However, there are substantial problems with current adjuvant formulations ranging from negative side effects to the inefficient induction of durable immunity. Therefore much current research is devoted to the identification of new adjuvants that will safely induce the type of immune response that will most effectively deal with its target. One of the challenges in this regard is that the precise modes of action of many adjuvants are not known. For example, the mode of action of alum, an adjuvant that has been used in vaccines since the 1930s and generates excellent antibody responses, is still inadequately understood. Therefore, this Keystone Symposia meeting on The Modes of Action of Vaccine Adjuvants will focus on the cell and molecular mechanisms of action of old and new adjuvants and other immunomodulatory agents and their use in various vaccines against infectious diseases and cancer. The general topic of this meeting is relevant to the NIAID mission with respect to the development of new candidate vaccine adjuvants.